Interstitial cystitis is an disorder of the bladder, which is accompanied by urinary urgency, pollakiuria and pain in the abdominal region and perineal region but is not accompanied by infections and particular pathologic findings. Interstitial cystitis causes very serious symptoms among the cystitis, which shows inflammation of the entire bladder wall extending not only to the mucous membrane but also to the muscle layer. Regarding the cause, breakdown of the bladder mucous membrane barrier function, elongation of a sensory nerve, C fiber, toward the mucous membrane side, concern of mast cell in the vicinity of C fiber, and the like have been suggested (cf., Non-patent Reference 1).
As the agent for treating interstitial cystitis, oral administration of a tricyclic antidepressant, an antihistaminic, a steroid, suplatast tosilate, pentosan polysulfate sodium, a Ca antagonist or the like, intravesical instillation therapy of heparin, hyaluronic acid, dimethyl sulfoxide (DMSO), capsaicin, resiniferatoxin or the like, and the like are generally used.
Among these, it is considered that the functional mechanism of capsaicin and resiniferatoxin is desensitization of C fiber, namely capsaicin-sensitive sensory nerve, and it has been reported that guinuclidin-3′-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate having a muscarine M3 receptor-selective binding activity has a capsaicin-sensitive sensory nerve inhibitory action (cf., Patent Reference 1).
By the way, it has been reported that a phenoxyacetic acid derivative represented by a general formula (I) or a pharmacologically acceptable salt thereof or a hydrate or solvate thereof has a selective β3-adrenoceptor stimulating activity and therefore is useful as a preventive or therapeutic agent for diseases caused by obesity, hyperglycemia or acceleration of movement of intestine and diseases caused by pollakiuria, urinary incontinence, depression, gallstone or acceleration of biliary movement (cf., Patent Reference 2). However, there are no report or suggestion on the relationship between phenoxyacetic acid derivatives and capsaicin-sensitive sensory nerve inhibiting activity.
wherein R1 represents hydroxyl group or a lower alkoxy group.
Non-patent Reference 1: Hainyo Shogai Practice (Urinary Disturbance Practice), published by Medical Review, 2004, Vol. 12, No. 1.
Patent Reference 1: International Publication WO 03/006019
Patent Reference 2: International Publication WO 00/02846